Imidazole → HCID 67006940, compound

HRID 2388417Notes

Reaction equation

HRID 2388417 reaction equation
[Cl:1][C:2]1[C:3]([CH3:29])=[C:4]([NH:10][C@H:11]([C@@H:26]([OH:28])[CH3:27])[C:12]([NH:14][NH:15][C:16](=[O:25])[C:17]2[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][CH:18]=2)=[O:13])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[CH3:30][C:31]([Si:34](Cl)([CH3:36])[CH3:35])([CH3:33])[CH3:32].N1C=CN=C1>>[Si:34]([O:28][C@@H:26]([CH3:27])[C@@H:11]([NH:10][C:4]1[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([Cl:1])[C:3]=1[CH3:29])[C:12]([NH:14][NH:15][C:16](=[O:25])[C:17]1[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][CH:18]=1)=[O:13])([C:31]([CH3:33])([CH3:32])[CH3:30])([CH3:36])[CH3:35]

Participants

4

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 67006530HCID 67006530, compound

Product 1

HCID 67006940HCID 67006940, compoundYield 84%

Procedure

N′-((2R,3S)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)-4-cyano benzohydrazide (12.1 g, 29.3 mmol) was reacted with TBDMSCl (13.2 g, 88.0 mmol) and imidazole (68.1 g, 146.0 mmol) in a manner analogous to that described for the preparation of intermediate 7b. Purification of the compound was accomplished by pouring the reaction mixture into ice-cold water and filtering off the solid precipitate. This was taken up in methylene chloride (400 mL) and sequentially washed with water (2×100 mL) and brine (100 mL). This was dried over sodium sulfate, filtered and concentrated down to roughly 100 mL. Hexanes were then added producing a white solid. This was filtered out and washed with hexanes to give the product as a white solid (12.92 g, 84%). 1H NMR (400 MHz, CDCl3, δ in ppm) 9.32 (m, 2H), 7.89 (AA′XX′, J=8.4 Hz, 2H), 7.71 (AA′XX′, J=8.6 Hz, 2H), 7.37 (d, J=8.4 Hz, 1H), 6.47 (d, J=8.8 Hz, 1H), 5.37 (d, J=6.2 Hz, 1H), 4.49 (m, 1H), 3.99 (m, 1H), 2.33 (s, 3H), 1.25 (d, J=6.2 Hz, 3H), 0.92 (s, 9H), 0.14 (s, 3H), 0.09 (s, 3H).

Workup

  1. customPurification of the compound
  2. additionby pouring the reaction mixture into ice-cold water
  3. filtrationfiltering off the solid precipitate
  4. washsequentially washed with water (2×100 mL) and brine (100 mL)
  5. dry with materialThis was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated down to roughly 100 mL
  8. additionHexanes were then added
  9. customproducing a white solid
  10. filtrationThis was filtered out
  11. washwashed with hexanes

Sources & evidence

ORD record
ord-f3b8c8d2f33f471393fe93bed802a0ff
Source dataset
uspto-grants-2012_09
Patent number
US08268872B2

Reaction notes

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